Arvanil reverses cisplatin resistance in ovarian cancer by activating HMOX1-driven ferroptosis.

Cisplatin resistance limits the effectiveness of ovarian cancer (OC) therapy. Arvanil is a synthetic capsaicin derivative with favorable pharmacokinetic properties. This study showed that Arvanil enhances the anti-tumor effect of cisplatin in cisplatin-resistant ovarian cancer cells, partly associated with HMOX1-related ferroptosis. The combination treatment elevated reactive oxygen species (ROS), lipid peroxidation (LPO), and ferrous ion (Fe²⁺) levels, suppressed GPX4 protein expression, and activated multiple key ferroptosis regulators. Inhibition of HMOX1 partially reversed these effects, confirming its pivotal regulatory role. In vivo experiments further validated the synergistic anti-tumor efficacy of the Arvanil-cisplatin combination, with no significant changes in body weight and no apparent histopathological or serum biochemical abnormalities detected under the tested conditions. This study provides a novel strategy to overcome cisplatin resistance and expands the potential application of small-molecule ferroptosis inducers in cancer therapy.